THU0110 DIAGNOSTIC ISSUES IN DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS: PRELIMINARY RESULTS OF A SYSTEMATIC LITERATURE REVIEW INFORMING THE 2020 EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS
Authors: N. M. T. Roodenrijs, M. Kedves, A. Hamar, G. Nagy, J. M. Van Laar, D. Van der Heijde, P. Welsing
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) patients treated according to European League Against Rheumatism (EULAR) recommendations failing ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) with a different mode of action who still have complaints which may be suggestive of active disease may be defined as suffering from ‘difficult-to-treat RA’. Before switching to another DMARD in these patients, the diagnosis of RA and the presence of inflammatory activity should be verified to prevent possible over- and under treatment. Objectives: To systematically summarise evidence in the literature on diagnostic issues regarding (mis-)diagnosis of RA and mimicking diseases, and assessment of inflammatory disease activity in difficult-to-treat RA patients, informing the 2020 EULAR recommendations for the management of difficult-to-treat RA. Methods: A systematic literature search was performed: PubMed and Embase databases were searched up to December 2018. Relevant papers were selected and appraised (Figure 1). Results: Regarding (mis-)diagnosis of RA and its differential diagnoses, four studies were selected (Figure 1a): one assessed the diagnosis of RA and three focused on coexisting mimicking diseases (fibromyalgia and bacterial infection). No diagnostic tests were replicated. For evaluation of inflammatory activity in RA, and specifically the effect of comorbidities on assessing inflammatory activity, 63 and five studies, respectively, were included (Figure 1b). At patient level, ultrasonography (US) scores were related to composite indices (range of correlations (r): 0.25-0.70) and swollen joint counts (range r: 0.33-0.78). A multi-biomarker disease activity score (range r with composite indices: 0.41-0.52) and optical spectral transmission measures (range r with US: 0.54-0.64) were promising measures, but cut-offs are preliminary. At joint level, US was related to MRI (range of sensitivity 64-91% and specificity 60-94% for synovitis) and histology (range r: 0.52-0.65 for inflammation). Concomitant obesity and fibromyalgia may lead to overestimation of disease activity according to composite indices, US may be used to assess inflammatory activity in these patients. Conclusion: This SLR highlights the gap of knowledge in the optimal confirmation of a (mis-)diagnosis of RA or diagnosis of mimicking diseases in difficult-to-treat RA patients. Current evidence for optimal assessment of inflammatory activity when there is doubt based on clinical assessment and composite indices is limited. Most studies reported correlations which are not directly useful in clinical practice to determine presence or absence of inflammatory activity. The evidence will be updated up to December 2019. Currently, US seems the most accurate measure to evaluate the presence of inflammation in difficult-to-treat RA patients, including those with concomitant obesity or fibromyalgia. Disclosure of Interests: Nadia M. T. Roodenrijs: None declared, Melinda Kedves: None declared, Attila Hamar: None declared, György Nagy: None declared, Jacob M. van Laar Grant/research support from: MSD, Genentech, Consultant of: MSD, Roche, Pfizer, Eli Lilly, BMS, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Paco Welsing: None declared